7-129648270-T-C

Position:

• chr7-129648270-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005011.5(NRF1):​c.-6-9076T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 147,118 control chromosomes in the GnomAD database, including 2,712 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2712 hom., cov: 29)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

Genes affected

NRF1 (HGNC:7996): (nuclear respiratory factor 1) This gene encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternative splicing results in multiple transcript variants. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRF1	NM_005011.5	c.-6-9076T>C		intron_variant		ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.-9-9073T>C		intron_variant			NP_001280092.1
NRF1	NM_001040110.2	c.-9-9073T>C		intron_variant			NP_001035199.1
NRF1	NM_001293164.2	c.-377-9073T>C		intron_variant			NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.-6-9076T>C		intron_variant		1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 26575 AN: 147044 Hom.: 2702 Cov.: 29

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 26586 AN: 147118 Hom.: 2712 Cov.: 29 AF XY: 0.182 AC XY: 12970 AN XY: 71232

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.162

Alfa AF: 0.177 Hom.: 301

Bravo AF: 0.188

Asia WGS AF: 0.364 AC: 1260 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11487138; hg19: chr7-129288110;